This program is aimed at ultimate palliation of the two most prevalent diseases of human hemoglobin: those involving sickle hemoglobin (Hb S), and the thalassemia syndromes. The intended mechanism of palliation is increased net synthesis of fetal hemoglobin (Hb F), to be achieved by augmentation of gamma-globin synthesis. The major specific aim is to examine concepts of genetic control of hemoglobin synthesis, with the hamster as an experimental animal model bearing a fetal hemoglobin fraction into adult life. Hormones suspected of exercising partial control of hemoglobin synthesis will be tested in adult hamsters and in preparations of hamster fetal liver erythroid cells. Relative rates of synthesis of adult and fetal hemoglobins will be examined, and evidence for altered relative rates will be pursued in erythroid cell suspensions. Assays for hormone influence in vitro will include measurements of rates of synthesis of globin and hemoglobin, and characterization of nuclear non-histone protein, a possible regulator of gene activation. The ultimate clinical goal is control of hemoglobin synthesis in human disease states.